Having carved out a truly unique niche in “high-throughput” microbiology, Biolog, of Hayward, Calif., is now seeking to broaden its flagship technology — the Phenotype MicroArray — to encompass mouse, human, and other mammalian cell lines.
The Phenotype MicroArray (PM) technology allows researchers to simultaneously assess as many as 2,000 individual phenotypes in bacterial or fungal cells of interest using a standard 96-well assay plate in combination with the OmniLog, the company’s cell incubator-cum fluorescence plate reader.
The company, which was founded almost 20 years ago, has been nearly unchallenged in the field of bacterial and fungal cell phenotyping, particularly since it first introduced the PM in 2001. According to Barry Bochner, the company’s vice president for research and development, the platform has two major uses: gene expression and drug response studies.
Regarding gene expression studies, Bochner said “a lot of people have found genes that could be promising drug targets, but don’t know what the gene does for sure. This provides a very direct biological assay for gene function.” In this type of assay, the company stresses the cell in a variety of ways; for instance, changing pH, temperature, or nutrient, salt, and metal availability.
For drug discovery, Bochner said that Biolog’s technology enables scientists to obtain a more complete picture of a drug’s effect on a specific microbial cell. “People usually do this type of assay on cells in a rapid growth state, and they’re only looking at the cell under one state,” he said. “But a cell is always changing — it is a dynamic entity. With our technology, you can take a drug and get a very information-rich fingerprint of its effect on the cell.”
Biolog has gotten this far on the technology, mostly because of its uniqueness in the marketplace. As compared to other high-throughput cellular analysis tools, the PM is competitively priced, as well. Timothy Mullane, Biolog’s president and CEO, said that a full set of assays for a bacterial strain costs between $500 and $700, while the OmniLog instrument is about $90,000.
The company says that several major pharmaceutical and biotechnology companies are testing the PM under license, and Bochner said that “most of our customers are some very prestigious labs in academia and government.”
But Biolog realizes the importance of teaming up with big pharma and biotech too, which is the main impetus for moving into mammalian cells.
“There is a big need and a much bigger market,” said Bochner. “One of the biggest problems that drug companies have is that they have thousands of redundant compounds.” He added that a mammalian cell array would likely carry cell lines representing different organs in the body.
According to Bochner, some of the initial ideas that the company has for applications include testing a drug’s mode of action and toxicology, or determining the effects of different combinations of drugs on various cell lines.
“Also, in manufacturing, people use human cell lines to make antibodies and other biological molecules,” he said. “We expect [a human cell array] to allow researchers to test cells over time. People don’t have really good tools to tell whether their cells are changing from day to day. This would be quality control for anybody doing cell-based assays, and will probably be the first application.”
Biolog has been beating the drums about mammalian cell arrays in its press releases for a few years, and there is no official word on exactly when the new platform will be unveiled. But Bochner told Inside Bioassays that the company expects to have human and other mammalian cell arrays by the end of this year.
The company currently has working prototypes that allow simultaneous assessment of up to 600 phenotypes. Bochner said that he expects that number to increase in the future. In addition, Mullane told Inside Bioassays that although the specifics have not yet been determined, he did not expect the shift to mammalian cell lines to dramatically affect the current price of the PMs and OmniLog system.
In the Works
Meanwhile, Biolog continues to rack up customers, mostly in academia or government, for its bacteria-based microarrays. Last Thursday, the company announced that Lawrence Livermore National Laboratory has begun using the Phenotype MicroArray for high-throughput research on pathogens that are of interest in biodefense.
This announcement comes on the heels of a similar one two weeks ago, which said Lawrence Berkeley National Laboratory is using the Phenotype MicroArray to investigate bacteria — specifically Desulfovibrio vulgaris — that are of interest to environmental scientists because of their ability to reduce sulfates and toxic metals.
One of the most loyal customers of the technology is the Institute for Genomic Research, which Biolog signed on in 2002. Ian Paulsen, an associate investigator at TIGR, leads a team of scientists whose research focuses on comparative genomic and functional analysis of microbial pathogens. Although Paulsen is leading projects involving several microorganisms, he said that the group has been particularly interested in Pseudomonas aeruginosa, an opportunistic pathogen most notorious for causing severe complications in cystic fibrosis patients.
“We’ve been able to determine the function of a number of genes whose function was previously unknown,” said Paulsen.
He added that they use Biolog’s technology because “there’s almost no alternative. The only real alternative is the labor-intensive process of making up hundreds or thousands of culture plates with different conditions. For doing high-throughput phenotypic analysis, theirs is the only one.”
Bochner agreed that Biolog doesn’t really have major competitors. “A lot of people are doing cell-based assays,” he said, but added that none provide the same type of comprehensive cellular analysis that the Phenotype MicroArray does.
“You can do similar things with gene chips,” he added, “but the problem is … so many things change … and it’s hard to tell which changes are the really interesting, biologically significant changes. Because [the PM] is a biological assay, we can detect a change only when there is a biological change. So our technology is pre-filtered for biological relevance, in a sense.”